Systemic perturbation of cytokine and chemokine networks in Erdheim-Chester disease: a single-center series of 37 patients

Immunopathogenesis of Erdheim-Chester disease (ECD), a rare non-Langerhans cell histiocytosis, is poorly known. In previous studies, various cytokines were detected in ECD lesions, presumably orchestrating lesional histiocyte recruitment. Because ECD lesions are frequently associated with systemic symptoms, we postulated that underlying global immune perturbations might also be revealed. We quantitatively analyzed 23 cytokines in serum samples obtained from a large single-center cohort of 37 patients with ECD, and studied the impact of treatment on cytokine production. IL-6, IL-12, interferon-alpha (IFN-alpha), and monocyte chemotactic protein-1 (MCP-1) levels were significantly higher in untreated patients than in controls, whereas interferon-gamma (IFN-gamma) inducible protein 10, IL-12, MCP-1, and IL-1 receptor antagonist were found significantly increased in IFN-alpha-treated patients. A biomathematical approach was used to rationalize multiparameter data, to generate new hypotheses, and identify global control pathways. Interestingly, cytokine profiles proved to be particularly stable at the individual level, and an "ECD signature" further distinguished patients from controls, based on their production of IFN-alpha, IL-12, MCP-1, IL-4, and IL-7. Altogether, our data underline the systemic immune Th-1-oriented perturbation associated with this condition and provide clues for the choice of more focused therapeutic agents in this rare disease with noncodified therapeutic management. (Blood. 2011;117(10):2783-2790)